I don't understand any of the technical jargon here, but kind of highlights all of the different things going on with the company. There is a shareholders meeting on July 14, and hopefully we will hear some good news before then.
Valued Shareholders:
We would like to profile the Company progress over the 2nd calendar quarter of this year. We continue to make scientific progress as demonstrated by our scientists? published papers in respected scientific journals. As a matter of maintaining scientific integrity, papers in scientific journals are reviewed and approved for publication by committees of independent scientists. This is tangible evidence that the Company?s research is highly relevant.
Publications and Scientific Meetings:
1. Tan, X., Actor, J.K., & CHEN. Y., PNA Antisense Oligomer as a Therapeutic Strategy against Bacterial Infection: Proof of Principle Using Mouse Intraperitoneal Infection Antimicrobial Agent and Chemotherapy, (accepted for publication), 2005.
2. Tan, X. & CHEN, Y., A novel genomic approach identifies bacterial DNA-dependent RNA polymerase as the target of an antibacterial oligodeoxynucleotide, RBL-1 Biochemistry, 44:6708-6714, 2005.
3. Tan, X., Knesha, R., Margolin, W. & CHEN, Y. DNA enzyme generated by a novel single-stranded DNA expression vector inhibits expression of the essential bacterial cell division gene ftsZ, Biochemistry, 43:1111-1117, 2004.
4. CHEN, Y., Tan, X., and McMicken, H. ?In vivo generation of oligodeoxynucleotides for regulating gene expression?. Keystone Symposia, New Advances in Drug Discovery, March 21-26, 2004, Keystone, Colorado.
5. CHEN, Y. ?A Novel Single-Stranded DNA Expression Vector?. Louisiana at the Crossroads:
Moving Biotechnology from Research to Commercialization, Shreveport, LA, June 24, 2004 (invited speaker).
Sponsored Research Agreements/Collaborations
Sponsored and collaborative research are very effective and economical methods of employing top-notch scientific talent and expensive facilities for a fraction of the cost if we were to replicate these efforts in-house. Sponsored research is paid for by the Company. In collaborative research, one party may provide technology and the collaborating party may use the technology in an investigation. The following is a summary of sponsored and collaborative research projects in progress. The fees charged by the institutions total less than $150,000.
1) Dr. Cy Stein (Albert Einstein Medical School/Montefiore Medical Center) has constructed melanoma stable cell lines with significant reduction of apoptotic gene, Bcl-2, expression at both mRNA and protein levels. The biological analysis of these cell lines has been completed. The next step will be to conduct in vivo (animal) experiments to study the effects of CytoGenix antisense clones on cancers transplanted into mice. Louisiana State University Health Science Center
2) Dr. Frank Orson (Baylor College of Medicine) is currently conducting an in vivo study to use aerosol delivery of the ssDNA expression vector targeting pKC-alpha, an oncogene associated with lung cancer. Several variations in delivery methods are being tested including polyethylenimine (PEI) with plasmid IP, naked plasmid ID and PEI aerosol.
3) Dr. Michael Mathis (Louisiana State University Health Science Center) is currently constructing single-stranded DNA adenoviral expression vector.. He is planning to use this vector to target eIF4E in head and neck cancer therapy.
4) Drs. Edward Mason and Jesus Vallejo (Texas Children Hospital, Baylor College of Medicine) are investigating Peptide Nucleic Acid compounds as therapeutics for bacterial resistant strains such as Methicillin resistant Staphylococcus Aureus (MRSA) and Vancomycin resistant Staph (VRSA) using a mouse model.
5) Dr. David Weiner (University of Pennsylvania Medical School) is conducting animal studies using Cytogenix? synthetic DNA to test the immunological activity of a DNA vaccine against small pox.
6) Under Agreement, the Company has provided synthetic DNA to test the immunological activity of a DNA vaccine against Hepatitis B.
7) Under Agreement, the Company has provided synthetic DNA to test the immunological activity of a DNA vaccine against Flu.
8) The Company licensed a compound from the National Institutes of Health (NIH) to prepare a synthetic DNA construct to test a DNA vaccine against HIV.
9) Dr. Jeffrey Actor (University of Texas Health Science Center-Houston). has completed a study investigating peptide nucleic acid (PNA) antisense oligomers as therapeutic agents against bacterial infection in a mouse peritonitis model. The PNA treatment was sufficient to rescue up to 100% of the bacterial infected animals. This work will be published in the journal of Antimicrobial Agent and Chemotherapy in October of 2005.
10) Negotiations are being conducted for sponsored research on mechanistic studies to demonstrate proof of biologic activity of the anti-inflammatory compound (CY303)
Product Development:
1) Herpes/Simplivir: primary vendors and back-ups have been identified, experimental protocols defined and budgets prepared for studies needed to complete the IND application to the FDA. These include:
* Bio-distribution studies ;
* GLP Toxicology;
* DNA drug substance determination; and
* SIMPLIVIR drug product.
Vendor selection and project initiation await funding.
2) Anti-microbials: We have tested two anti-microbial compounds against gene targets; one in Escherichia Coli and the other in Staphylococcus Aureus. These compounds were made using different chemical backbones than the usual sugar molecules in standard DNA. The backbone is the structure used to support the oligonucleotide sequence designed to down-regulate a particular gene target.
Thirteen (13) additional gene targets in Methicillin resistant Staphylococcus (MRSA) have been identified using the Company?s screening technology. The oligos against these targets are being tested in our laboratory. Sequences showing anti-microbial activity will be tested in animals at Texas Children?s.
Negotiations are being conducted to obtain the rights to use a further identified alternative backbone in combination with the sequences we have discovered and found successful.
3) (SynDNA) Facility: Alfa Laval Biokinetics has completed a feasibility study for design and construction of the facility. The feasibility study includes timeline and cost estimates. The Phase I Engineering Study has also been completed.
Intellectual Property:
New U.S. patent application, ?Cell Free Biosynthesis of High-Quality Nucleic Acid and Uses Thereof?
New U.S. Continuation-in Part (CIP) application to strengthen enablement combining:
?In Vivo ssDNA Expression Vectors? together with
?Identification of Novel Anti-Bacteria Agents by Screening the Single-
stranded DNA Expression Library? and
?Nucleotides for Prevention and Treatment of Bacterial and Fungal Pathologies?
National Filings in eight (8) countries under the Patent Cooperation Treaty (PCT) of the U.S. patent application, ?Treatment of HSV-Related Pathologies Using ssDNA?
We look forward to continuing this work and appreciate your continuing support.
Very truly yours,
Malcolm Skolnick
